Born in Newcastle-under-Lyme, Brittain was the daughter of a well-to-do family who owned paper mills in Hanley and Cheddleton. She had an uneventful childhood with her only brother her closest companion. At 18 months her family moved to Macclesfield, Cheshire and when she was 11 they moved again, to Buxton in Derbyshire. From the age of thirteen she attended boarding school at St Monica's, Kingswood in Surrey where her aunt was principal. Studying English Literature at Somerville College, Oxford, she delayed her degree after one year in the summer of 1915 in order to work as a V.A.D. nurse for much of the First World War. Her fiancé Roland Leighton, two other close friends Victor Richardson and Geoffrey Thurlow, and her brother Edward Brittain MC were all killed during the war. Their letters to each other are documented in the book Letters from a Lost Generation.

Returning to Oxford after the war to read History, Brittain found it difficult to adjust to life among the postwar generation. It was at this time she met Winifred Holtby, and a close friendship developed with both aspiring to become established on the London literary scene. The bond lasted until Holtby's death in 1935.

In 1925 Brittain married George Catlin, a political scientist and philosopher. Their son, John Brittain-Catlin (1927—1987), was an artist painter, businessman, and the author of the autobiography Family Quartet, which appeared in 1987. Their daughter, born in 1930, is the former Labour Cabinet Minister, now Liberal Democrat peer, Shirley Williams.

Brittain's first published novel was The Dark Tide (1923). It was not until 1933 that she published Testament of Youth, which was followed by the sequels, Testament of Friendship (1940) — her tribute to and biography of Winifred Holtby — and Testament of Experience (1957), the continuation of her own story, which spanned the years between 1925 and 1950. Vera Brittain wrote from the heart and based many of her novels on actual experiences and actual people. In this regard her novel Honourable Estate (1936) was in part more of a memoir.

In the 1920s she became a regular speaker on behalf of the League of Nations Union, but in June 1936 she was invited to speak at a peace rally in Dorchester, where she shared a platform with Dick Sheppard, George Lansbury, Laurence Housman and Donald Soper. Afterwards Sheppard invited her to join the Peace Pledge Union, and following six months' careful reflection she replied in January 1937 to say she would. Later that year Brittain also joined the Anglican Pacifist Fellowship. Her newly found pacifism came to the fore during World War II, when she began the series of Letters to Peacelovers.

She was a practical pacifist in the sense that she helped the war effort by working as a fire warden and by travelling around the country raising funds for the Peace Pledge Union's food relief campaign. She was vilified for speaking out against saturation bombing of German cities through her 1944 booklet Massacre by Bombing. Her principled pacifist position was vindicated somewhat when, in 1945, the Nazis' Black Book of 2000 people to be immediately arrested in Britain after a German invasion was shown to include her name.

In November 1966 she suffered a fall in a badly lit London street while on the way to a speaking engagement. She fulfilled the engagement but afterwards found she had suffered a fractured left arm and broken little finger of her right hand. These injuries began a physical decline in which her mind became more confused and withdrawn.Vera Brittain never fully got over the death of her brother Edward. When she died in Wimbledon on 29 March 1970, aged 76, her will requested that her ashes be scattered on Edward's grave on the Asiago Plateau in Italy — "...for nearly 50 years much of my heart has been in that Italian village cemetery". Her daughter honoured this request in September 1970.

She was portrayed by Cheryl Campbell in the 1979 BBC2 television adaptation of Testament of Youth.

Songwriter and fellow Anglican Pacifist Fellowship member Sue Gilmurray wrote a song in Brittain's memory, titled "Vera".

In 1998 Brittain's First World War letters were edited by Alan Bishop and Mark Bostridge and published under the title Letters from a Lost Generation. They were also adapted by Bostridge for a Radio Four series starring Amanda Root and Rupert Graves.

Because You Died, a new selection of Brittain's First World War poetry and prose, edited by Mark Bostridge was published by Virago in 2008 to commemorate the ninetieth anniversary of the Armistice.

On 9 November 2008, BBC One broadcast an hour-length documentary on Brittain as part of its Remembrance Day programmes hosted by Jo Brand.

In February 2009, it was reported that BBC Films is to adapt Brittain's memoir, Testament of Youth, for the cinema.